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Biomedical subjects

Johanna Tischer

Publications and source records attributed to Johanna Tischer.

6 recordsLinked to original sources

A comparison of donor lymphocyte infusions or imatinib mesylate for patients with chronic myelogenous leukemia who have relapsed after allogeneic stem cell transplantation.

Imatinib mesylate is highly effective in relapsed chronic myelogenous leukemia (CML) after allogeneic hematopoetic stem cell transplantation (HSCT). However, it is unknown whether imatinib produces durable molecular remissions. The outcome of CML patients transplanted at our center who had received only imatinib for relapse after HSCT was compared with that of patients treated with donor lymphocyte infusions (DLI). Imatinib therapy resulted in a higher incidence of relapse and inferior leukemia-free survival (p=0.006 and p=0.016, respectively). These data suggest that imatinib alone probably does not cure relapse after HSCT.

Adult↗

Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation.

A sequential regimen of chemotherapy, reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation (SCT), and prophylactic donor lymphocyte transfusion (pDLT) was studied in 103 patients with refractory acute myeloid leukemia (AML). According to published criteria, refractoriness was defined by primary induction failure (PIF; n = 37), early (n = 53), refractory (n = 8), or second (n = 5) relapse. Chemotherapy consisted of fludarabine (4 x 30 mg/m(2)), cytarabine (4 x 2 g/m(2)), and amsacrine (4 x 100 mg/m(2)), followed 4 days later by RIC, comprising 4 Gy total body irradiation (TBI), cyclophosphamide, and antithymocyte globulin. Patients without graft-versus-host disease (GvHD) at day +120 received pDLT in escalating doses. Patients' median age was 51.8 years. Before conditioning, 99 patients had active disease, 3 were aplastic, 1 was in second complete remission (CR2). Forty-one patients had family donors, 62 had unrelated donors. With a 25-month median follow-up, overall survival (OS) at 1, 2, and 4 years was 54%, 40%, and 32%; the respective leukemia-free survival (LFS) was 47%, 37%, and 30%. Patients with PIF showed a 2-year OS of 62.5%. OS was 87% in 17 patients receiving pDLT. One-year cumulative incidence of leukemic death and non-relapse-mortality was 28.7% and 17.2%. In a multivariate analysis, more than 2 courses of prior chemotherapy were the strongest predictor for poor outcome (P = .007; HR = 3.01 [OS]; P = .002; HR = 3.25 [LFS]). These results indicate a high activity of the regimen in refractory AML.

Acute Disease↗

Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome.

PURPOSE: To improve the effect of allogeneic stem-cell transplantation by sequential use of intensive chemotherapy, reduced-intensity conditioning (RIC), and prophylactic donor lymphocyte transfusions (pDLTs) in high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). PATIENTS AND METHODS: In a prospective study of 75 consecutive patients (median age, 52.3 years), high risk was defined by progressive or refractory disease (n = 59), second remission after early relapse (n = 8), or first remission with poor prognosis based on cytogenetics or delayed response to induction therapy (n = 8). Unfavorable karyotypes were found in 49% of informative patients, and 68 patients had medical contraindications against standard conditioning. Fludarabine (30 mg/m2), cytarabine (2 g/m2), and amsacrine (100 mg/m2) for 4 days were used for cytoreduction. After 3 days of rest, RIC consisted of 4 Gy total-body irradiation, antithymocyte globulin, and 80 to 120 mg/kg cyclophosphamide. Thirty-one patients had an HLA-identical sibling donor; 44 patients had an unrelated and/or HLA-mismatched donor. pDLT was given from day +120 in patients who were not receiving immunosuppression and were free of graft-versus-host disease (GvHD). RESULTS: Complete remission was induced in 66 patients (88%). With a median follow-up of 35.1 months (range, 13.6 to 47.6 months), 2-year overall and leukemia-free survival were 42% and 40%, respectively. Outcome of patients with refractory disease or with complex cytogenetic aberrations was identical to that of better prognostic subgroups. Survival was best in patients who received high CD34+ cell numbers, and in patients with limited GvHD. CONCLUSION: Sequential use of intensive chemotherapy, RIC transplantation, and pDLT represents a promising approach to the treatment of high-risk AML and MDS, particularly in patients with most unfavorable prognoses.

Adolescent↗

In-vivo generation of leukaemia-derived dendritic cells.

Adoptive immunotherapy with transfusion of donor lymphocytes in allogeneic stem cell chimeras has been successful in the treatment of recurrent chronic myelogenous leukaemia (CML) and some patients with acute myeloid leukaemia (AML). The hypothesis that the graft-vs-leukaemia effect (GVL) is promoted by leukaemia-derived dendritic cells has been supported by the concurrent treatment of patients with cytokines that are known to induce differentiation of leukaemia cells towards dendritic cells. In combination with donor lymphocyte transfusions, treatment with interferon-alpha and granulocyte-macrophage colony-stimulating factor has been studied in patients with recurrent CML and AML, and pre-emptively in patients with high-risk AML. Long-term remissions have been observed in cytokine-treated patients, indicating the beneficial effect of cytokine stimulation of GVL reactions. This is likely to be due to differentiation of leukaemia progenitor cells towards dendritic cells in vivo.

Cell Lineage↗